靳衡-CSCIED科技核心评价数据库-手机版

单位：天津医科大学总医院

研究方向：

社会任职

个人介绍

高被引文献
最新文献
合作学者

1. Azathioprine Ameliorates Cellular Senescence in Rhabdomyolysis-Induced Acute Kidney Injury by Inhibiting the Vav1/Rac2/NF-κB Pathway in Macrophages

[学者论文] RS评分：0

作者： Heng Jin

《European Journal of Pharmacology》2026年 1011卷期

摘要：Background and purpose Rhabdomyolysis (RM) and rhabdomyolysis-induced acute kidney injury (RM-AKI) are increasingly prevalent, yet specific therapies are lacking.Cellular senescence contributes to the transition of RM-AKI to chronic kidney disease (CKD), in which macrophage–tubular epithelial interactions play a pivotal role. Azathioprine, an immunosuppressant, through its metabolite 6-thio-GTP, inhibits Vav1-mediated Rac2 activation; nevertheless, its potential role in RM-AKI has not been elucidated. This study explores the Vav1/Rac2/NF-κB pathway in macrophage-mediated senescence in RM-AKI and azathioprine's efficacy. Experimental approach A glycerol-induced RM-AKI mouse model was used. High-throughput RNA sequencing, proteomic profiling, and co-immunoprecipitation were performed to evaluate activation of the Vav1-associated pathway. RAW264.7-TCMK-1 co-cultures verified azathioprine's effects on the pathway and senescence. Key results RM-AKI mice showed renal senescence (elevated p53, p21, p16, SA-β-gal) and activated macrophage Vav1/Rac2/NF-κB. Azathioprine treatment down-regulated Vav1/Rac2 expression, improved renal function, and mitigated histological injury. In vitro, inhibiting the pathway reduced tubular senescence and improved LaminB1 integrity. Conclusion and implications Activation of macrophage Vav1/Rac2/NF-κB signaling promotes tubular cell senescence, whereas azathioprine counteracts this process by inhibiting the pathway.

关键词：Acute Kidney Injury

浏览量: 41 下载: 0 发表时间：2026/1/1 0:00:00

HTML阅读下载引用收藏
2. DOT1L regulates cellular senescence during the progression from acute kidney injury to chronic kidney disease via the micro-222-5p/WNT9B signaling pathway

[学者论文] RS评分：0

作者： Heng Jin

《American Journal of Nephrology》2025年 56卷 5期

摘要：Introduction: Acute kidney injury (AKI) is a common clinical condition where cellular senescence plays a crucial role in its progression. Previous studies have suggested that DOT1L plays a pivotal role in cellular senescence, yet its specific mechanisms in regulating AKI cellular senescence remain unclear. Methods: This study utilized a glycerol-induced in vivo AKI model and employed the DOT1L-specific inhibitor EPZ004777 (EPZ) to suppress DOT1L function. Aging staining, periodic acid-Schiff staining, and Masson staining were employed to assess renal aging, injury, and interstitial fibrosis. In vitro experiments utilized doxorubicin-treated human renal tubular epithelial (HK-2) cells to establish an AKI cellular senescence model. EPZ was used to inhibit DOT1L, evaluating its impact on cellular senescence. High-throughput miRNA sequencing was performed to analyze differential expression of miRNAs downstream of DOT1L, and DOT1L overexpression and dual luciferase reporter gene experiments were conducted to explore interactions among DOT1L, miR-222-5p, and Wnt family member 9B (WNT9B). Results: The results demonstrated that in vivo inhibition of DOT1L significantly reduced cellular senescence and improved renal tubular injury and interstitial fibrosis. In the doxorubicin-induced HK-2 cell model, DOT1L inhibition markedly decreased cellular senescence and lowered mRNA and protein levels of senescence markers while alleviating cell cycle arrest. DOT1L inhibition notably upregulated miR-222-5p expression and suppressed WNT9B expression, with opposite effects observed with DOT1L overexpression. Conclusion: DOT1L regulates cellular senescence through the miR-222-5p/WNT9B pathway in AKI. These findings suggest that DOT1L may serve as a potential therapeutic target to mitigate the progression of AKI to chronic kidney disease.

关键词：Acute Kidney Injury

浏览量: 36 下载: 0 发表时间：2025/2/1 0:00:00

HTML阅读下载引用收藏
3. IL-6/GATA2/SERPINE1 pathway is implicated in regulating cellular senescence after acute kidney injury

[学者论文] RS评分：0

作者： Heng Jin

《Frontiers in Molecular Biosciences Journal Default Logo Frontiers in Molecular Biosciences Are you an editor of this journal? Now editors can claim this journal on ResearchGate and gain exclusive stats and insights about its community. Learn more 1.3K journals in your field already have profiles. 》2025年 12卷期

摘要：Purpose: Acute kidney injury (AKI) secondary to Rhabdomyolysis syndrome represents a life-threatening complication, characterized by notably high incidence and mortality rates. The role of cellular senescence in the progression of AKI has increasingly garnered attention in recent years. Our previous research has demonstrated that remote ischemic postconditioning (RIPC) can attenuate renal cellular senescence and elevation of serum level of interleukin-6 (IL-6) induced by ischemia-reperfusion injury following crush injury. The objective of this study is to investigate the specific role of IL-6 in Rhabdomyolysis-induced AKI (RM-AKI).Methods: We established a mouse model of RM-AKI by intramuscular injection of glycerol and simulated RM-AKI at the cellular level by treating Hk-2 cells with myoglobin. Tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor, is a key substance. IL-6, a multifunctional cytokine, plays a crucial role in the occurrence and development of various kidney diseases. It can promote inflammatory responses, cell proliferation, fibrosis, and other processes. TCZ exerts a protective effect on the kidneys by specifically binding to the IL-6 receptor and blocking the signal transduction of IL-6. Additionally, the levels of IL-6 were detected by employing ELISA kits. RNA sequencing analysis was performed on cells treated with myoglobin and tocilizumab. Flow cytometry was utilized to assess cell cycle distribution and the percentage of senescent cells. The expression levels of SERPINE1, GATA2, p53, and p21 were determined by real-time quantitative PCR and Western blot. Additionally, a dual-luciferase reporter gene assay was conducted to validate the binding effect of SERPINE1 and GATA2.Results: Transcriptome Analysis revealed that genes including GATA2 and SERPINE1 were downregulated in HK-2 cells following tocilizumab treatment. Inhibition of the IL-6 receptor by tocilizumab in these cells led to a reduction in cellular senescence, accompanied by decreased of the cell cycle regulatory proteins P53 and P21 in mRNA and protein levels, while alleviating cell cycle arrest. Additionally, a dual-luciferase reporter assay confirmed that GATA2 binds to the promoter of SERPINE1 (PAI-1), thereby initiating its transcription.Conclusion: The IL-6/GATA2/SERPINE1 pathway mediates cellular senescence after acute kidney injury, and inhibiting IL-6 can alleviate AKI-induced cellular senescence, providing an important basis for exploring new therapeutic strategies.

关键词：Acute Kidney Injury

浏览量: 45 下载: 0 发表时间：2025/2/1 0:00:00

HTML阅读下载引用收藏

1. Azathioprine Ameliorates Cellular Senescence in Rhabdomyolysis-Induced Acute Kidney Injury by Inhibiting the Vav1/Rac2/NF-κB Pathway in Macrophages

2. DOT1L regulates cellular senescence during the progression from acute kidney injury to chronic kidney disease via the micro-222-5p/WNT9B signaling pathway

3. IL-6/GATA2/SERPINE1 pathway is implicated in regulating cellular senescence after acute kidney injury